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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated in rats, the effect of moderate hypothermia (30-31 degrees C) on extracellular levels of amino acids, with special emphasis on the excitatory amino acids (EAAs) glutamate and aspartate, lactate and pyruvate, after severe spinal cord compression. A laminectomy of Th7 and Th8 was made. A probe was inserted in a dorsal horn and microdialysis was performed for 1.5 h before and 4 h after applying severe compression for 5 min. Dialysate samples were collected at intervals of 10 min and analyzed by high-performance liquid chromatography. In normothermic (37.5 degrees C) animals there was a several-fold rise of glutamate that peaked in the first 10 min fraction after trauma. Hypothermic animals showed a similar increase after trauma, which was statistically significant until 20 min after injury. The level of glutamate was significantly higher in hypothermic animals from 20 to 70 min after injury, compared with normothermic animals. Aspartate also showed a marked increase following injury. The peak concentration was similar for both groups, whereas recovery was delayed in hypothermic animals. There was no significant difference between the normothermic and hypothermic animals for arginine, taurine, alanine, glutamine, histadine, glycine, threonine, tyrosine, and asparagine. No significant effect of hypothermia on lactate or lactate/pyruvate was noted. However, the mean level of lactate tended to be lower and recovery was quicker in hypothermic animals. The results of the present study suggest that moderate hypothermia does not attenuate extracellular accumulation of EAAs or markedly improve energy metabolism in our model. Instead, our findings raise the possibility that moderate hypothermia prolongs the duration of glutamate receptor overactivation. Since hypothermia effectively attenuates glutamate release in CNS and spinal cord ischemia models our results suggest different mechanisms of extracellular accumulation of EAAs in ischemia and trauma.
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PMID:Effects of moderate hypothermia on extracellular lactic acid and amino acids after severe compression injury of rat spinal cord. 904 12

Many glutamate antagonists have been reported to have a neuroprotective effect against ischemic brain damage; however, some of them have been also reported to induce hypothermia that confers remarkable neuroprotection against the damage. In order to avoid the confounding effects of hypothermia, we assembled a telemeter-based brain temperature control system that allows continuous monitoring and regulating of brain temperature during an ischemic insult and in the post-ischemic period in conscious and freely moving animals. Experiments were performed in gerbils that were subjected to administration of MK-801 (3, 5, and 10 mg/kg) and/or to 5-min ischemia. The system monitored continuous changes in brain temperature and regulated brain temperature at normothermic levels, revealing that a neuroprotective effect of 3 mg/kg MK-801 against ischemia-induced delayed hippocampal CA1 neuronal death was mainly due to hypothermia, whereas a high dose of MK-801 (5 and 10 mg/kg) produced a neuroprotective effect even when the brain temperature was maintained at normothermic levels. These results indicate that this system is very useful to test potential antiischemic agents, especially when the agents have hypothermic side effects.
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PMID:Continuous monitoring and regulating of brain temperature in the conscious and freely moving ischemic gerbil: effect of MK-801 on delayed neuronal death in hippocampal CA1. 905 37

Elevated levels of lactic acid can be deleterious to CNS tissue. Lactic acid is known to cause astroglial swelling and since glial swelling has been shown to inhibit L-glutamate (L-Glu) uptake, we examined whether one of the actions of lactic acid is to inhibit L-Glu uptake. Astrocyte cultures treated with lactic acid (25 mM; pH 6.1) showed an inhibition of L-Glu uptake by 65%. HCl (pH 6.1) also inhibited L-Glu uptake and this inhibition was potentiated by sodium lactate (25 mM). The inhibitory effect of lactic acid on L-Glu uptake was partially reversible and the reversibility was enhanced by hypothermia. Blocking glial swelling with D-mannitol, or treatment with antioxidants or hypothermia did not inhibit the effect of lactic acid on L-Glu uptake, indicating that swelling per se or free radicals, were not the factors in L-Glu uptake inhibition. Lactic acid induced a four-fold enhancement of L-Glu release and a seven-fold increase of K+ release. Our results suggest that lactic acid, by direct effect on pH, brings about a stimulation of K+ and L-Glu release which may be a factor in the inhibition of L-Glu uptake by lactic acid in astrocytes.
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PMID:Effect of lactic acid on L-glutamate uptake in cultured astrocytes: mechanistic considerations. 909 30

Effects of excitatory aminoacids (EAAs) aspartate (ASP) and glutamate (GLU) in a low (50 ng, i.c.) and high dose (20 micrograms, i.c.), were studied on nociception, catalepsy and rectal temperature in albino rats. Both ASP and GLU altered the tail flick reaction time to thermal stimulation in a dose dependent manner, increasing it with low doses and reduced with high doses. Naloxone (10 micrograms, ic) antagonized the anti-nociceptive effect of EAAs while ketamine (10 micrograms, ic)-a NMDA receptor antagonist antagonized the hyperalgesic effect. These EAAs also antagonized catalepsy induced by haloperidol, chlorpromazine, trifluoperazine and morphine. Both ASP and GLU produced a hyperthermic response in all animals, including those in which hypothermia was induced by reserpine. These EAAs produced a comparable central modulatory effects on nociception, catalepsy and core temperature.
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PMID:Effect of aspartate and glutamate on nociception, catalepsy and core temperature in rats. 914 55

Moderate hypothermia significantly diminishes consequences of spinal and cerebral anoxia. One component of this neuroprotection has been hypothesized to be suppression of excitotoxic transmitter release. Whether this suppression is attributable to reduced hypoxic injury that induces release or an alteration of the release process itself is unclear. We sought to characterize the temperature sensitivity (Q10) of basal and evoked calcitonin gene-related peptide (CGRP) and amino acid release from dorsal horn slices of rat spinal cord over a range of temperatures from 40 to 8 degrees C. At 40 degrees C, potassium (60 mM) and capsaicin (10 microM) evoked a 21- and 32-fold increase in basal CGRP concentrations, respectively. Capsaicin had no effect on glutamate release, but potassium evoked a 2.7-fold increase. Release evoked by either potassium or capsaicin was reduced in a biphasic fashion with declining temperature. Over the range of 40 to 34 degrees C, the Q10 values for evoked release for CGRP were 11.3 (potassium) and 39.7 (capsaicin) and for glutamate, 5. 5 (potassium). Over the range of 34 to 8 degrees C, Q10 values were near unity for all evoked release (0.8 and 1.3 for CGRP and 1.2 for glutamate). Although serine, glycine, glutamine, taurine, and citrulline showed no evoked release, basal levels were reduced at temperatures below 34 degrees C. The pronounced temperature dependency of evoked transmitter release between 40 and 34 degrees C is consistent with the profound cerebral protection observed with mild hypothermia in which metabolic activity is only slightly depressed.
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PMID:Temperature dependency of basal and evoked release of amino acids and calcitonin gene-related peptide from rat dorsal spinal cord. 915 57

Hypoxia-ischemia damages selected regions of the immature at different ages. Prior to 32 weeks gestation the periventricular white matter is selectively vulnerable but in the last trimester the basal ganglia become especially vulnerable to injury. Hypoxia-ischemia causes injury by activating a series of biochemical events that unfolds over a period of hours to days following the initial insult and we are investigating the ways in which age modifies these events. The cascade includes release of glutamate, overstimulation of excitatory amino acid receptors and raised intracellular levels of calcium. Clinically this series is manifested by hypoxic-ischemic encephalopathy (HIE), a syndrome that includes coma, seizures, a burst suppression EEG, respiratory depression and severe hypotonia. Clinical studies have established a relationship between the severity of neonatal encephalopathy and later manifestations of brain damage or cerebral palsy. Potential neuroprotective therapies need to be effective when given after the insult but the 'therapeutic time window' for most N-methyl-D-aspartate (NMDA) glutamate antagonists is limited after injury. Using a model of hypoxic-ischemic injury and neonatal rats and hypothermic-circulatory arrest in dogs, we found that immunohistochemical staining for neuronal nitric oxide synthase (nNOS) is markedly increased from 6 to 24 h after the insult in the basal ganglia and cortex. The induction of nNOS preceded the time of maximal neuronal necrosis and during the time when many apoptotic nuclei were appearing. We have also found that a brief period of 2 h of mild hypothermia (32 degrees C) following hypoxia-ischemia in neonatal rats delayed neuronal necrosis by more than a week. We are determining whether this delay is related to a change in nNOS activation. Induction of nNOS in the post-insult period may contribute to expression of injury and signs of encephalopathy following a hypoxic-ischemic insult.
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PMID:Hypoxic and ischemic disorders of infants and children. Lecture for 38th meeting of Japanese Society of Child Neurology, Tokyo, Japan, July 1996. 918 71

The exact mechanism of hypothermic cerebroprotection after traumatic brain injury (TBI) is not fully understood. The present study was conducted to investigate the effects of mild hypothermia on trauma-induced synthesis of nitric oxide (NO), which has been implicated in the pathogenesis of ischemic brain damage associated with glutamate neurotoxicity. Cerebral contusion was created in the rat parietal cortex by a weight-drop method, and extracellular concentrations of the NO end products nitrite and nitrate were measured using in vivo brain microdialysis and capillary electrophoresis under normothermic (37 degrees C) and mild hypothermic (32 degrees C) conditions. In normothermic animals, the level of NO end products increased markedly 10 min after contusion, reaching a maximum level at 20 min. In the hypothermic rats, such increases were absent. Although it is unknown whether endothelial NO synthase, neuronal NO synthase, or both caused the elevation of the NO end products seen in the normothermic animals, the present results indicate that inhibition of NO synthesis may play a part in hypothermic cerebroprotection following TBI.
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PMID:Effects of mild hypothermia on nitric oxide synthesis following contusion trauma in the rat. 919

Brain hypothermia during ischemia may have a neuroprotective effect on pathological and functional outcomes in vivo. Although a microdialysis study demonstrated that hypothermia decreases glutamate release into the extracellular space, the issue of whether this suppression of the glutamate elevation normally accompanying ischemia is attributable to inhibition of intra-ischemic release or acceleration of post-ischemic re-uptake was not addressed. Recently, we established a real-time method for monitoring glutamate levels in extracellular space, utilizing a dialysis electrode. This method allows detailed analysis of the in vivo dynamics of biphasic glutamate elevation in the extracellular space during the intra-ischemic period and post-ischemic re-uptake. The present results show that post-ischemic hypothermia has little effect on the initial glutamate release, but remarkably enhances post-ischemic glutamate re-uptake.
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PMID:Real-time monitoring of the effects of normothermia and hypothermia on extracellular glutamate re-uptake in the rat following global brain ischemia. 924 46

Agonists of the GABA-A receptor are neuroprotective after experimental stroke, but studies of GABA-B agonists have contradicted each other. To further investigate whether GABA-B agonists may be neuroprotective, we devised a quantal bioassay using the intraluminal occlusion method of inducing reversible cerebral ischemia. Subjects underwent middle cerebral artery occlusion for varying amounts of time, ranging from 5 to 90 min. Behavioral outcome was measured 48 h later with a quantal observational scale: score of abnormal given for any one of asymmetric forepaw flexion on tail lift, asymmetric grip, circling, reduced exploration, seizures, or death. To the grouped response data the logistic equation was used to find the ED50, the duration of occlusion that caused one-half of the subjects to be abnormal. To find the potency ratio for each drug, we divided the ED50 for treatment by that for vehicle. We administered baclofen, a GABA-B agonist, intraperitoneally 5 min after the onset ofischemia. Baclofen (20 mg/kg) was neuroprotective (potency ratio of 3.0, P < 0.05), but a lower dose (10 mg/kg) was not. However, both doses of baclofen caused significantly more intracerebral hemorrhages than control. In awake animals, both baclofen doses caused significant increases in mean arterial pressure, but no changes in other cardiorespiratory variables. The glutamate antagonist MK-801, the GABA-A agonist muscimol, and hypothermia were all protective using the bioassay (potency ratios ranging from 1.5 to 3.0). We conclude that although baclofen (20 mg/kg) may be neuroprotective, its utility is complicated by postischemic hypertension and cerebral hemorrhages.
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PMID:High dose baclofen is neuroprotective but also causes intracerebral hemorrhage: a quantal bioassay study using the intraluminal suture occlusion method. 934 59

Hypothermia applied after hypoxia offers neuroprotection in neonatal animals, but the mechanisms involved remain unknown. Hypoxia was induced in newborn piglets and changes in excitatory amino acids (EAAs) and the citrulline:arginine ratio (CAR) were followed by microdialysis for 5 h. After the 45 min hypoxic insult, the animals were randomized to receive normothermia (39 degrees C; n=7) or hypothermia (35 degrees C; n = 7). After reoxygenation, extracellular glutamate, aspartate and the excitotoxic index were significantly lower in the cerebral cortex of hypothermic animals than in normothermic animals. A progressive rise of the CAR occurred during reoxygenation in the normothermic group whereas the ratio tended to decrease in the hypothermic group. In conclusion, post-hypoxic hypothermia attenuated NO production and overflow of EAAs.
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PMID:Post-hypoxic hypothermia reduces cerebrocortical release of NO and excitotoxins. 935 72


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